tbuckley/cabot-search huggingface dataset:
Successful hemostasis using a self-assembling peptide hydrogel for bleeding after endoscopic papillary large-balloon dilation
Authors: Tadahisa Inoue, Mayu Ibusuki, Rena Kitano, Yuji Kobayashi, Kiyoaki Ito, Masashi Yoneda
Journal: Endoscopy (2023)

Adverse bleeding events can occur after endoscopic papillary large-balloon dilation (EPLBD) [1], though not as frequently as after endoscopic sphincterotomy. Post-EPLBD bleeding often originates from sites deeper than the bile duct orifice, such as lacerations of the bile duct wall, and the origin of bleeding may not be identified; therefore, it is often difficult to stop the bleeding. A novel self-assembling peptide hydrogel (PuraStat; 3-D Matrix, Tokyo, Japan) was recently developed as a hemostatic agent [2] [3] [4]. We present a case of hemostasis of massive post-EPLBD bleeding achieved with this hydrogel.
What Is the Optimal Way to Use Geriatric Assessment and Patient-Reported Outcomes in Older Patients With Advanced Cancer?
Authors: Takahiro Kaneko, Akihiko Shimomura, Chikako Shimizu
Journal: Journal of Clinical Oncology (2023)

Culakova et al 1 reported on the impact of a geriatric assessment (GA) intervention on the Patient-Reported Outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (CTCAE) by analyzing the GAP701 trial data.The authors showed that more than 80% of older patients with advanced cancer had at least one symptom at the start of systemic therapy and that GA intervention reduced the frequency of grade $ 2 symptomatic toxicities by 5.9% after 6 months of treatment.Thus, treatment decisions must be based not only on individual oncologists' judgment but also on GA and patients' reports of symptoms.However, there are several aspects that require clarification for a better understanding of this study.
Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation
Authors: Yingying Huo, Linjie Wu, Aiming Pang, Qing Li, Fang Hong, Caiying Zhu, Zining Yang, Weiqian Dai, Yawei Zheng, Qianqian Meng, Jiali Sun, Shihui Ma, Linping Hu, Ping Zhu, Fang Dong, Xin Gao, Erlie Jiang, Sha Hao, Tao Cheng
Journal: Science Immunology (2023)

Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted HSPCs underwent rapid and measurable changes during the first 30 days after transplantation, characterized by a strong proliferative response on the first day. Transcriptomic analysis of HSPCs enabled us to observe that immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family were enriched in granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) infused fewer S100Ahigh immunoregulatory neutrophil progenitors, immunophenotyped as Lin-CD34+CD66b+CD177+, than those who did not develop aGVHD. Therefore, our study provides insights into the regenerative process of transplanted HSPCs in human patients and identifies a potential criterion for identifying patients at high risk for developing aGVHD early after transplant.
Patient and public involvement within epidemiological studies of long COVID in the UK
Authors: Ash Routen, Lauren O’Mahoney, Olalekan Lee Aiyegbusi, Yvonne Alder, Amitava Banerjee, Lewis Buckland, Chris Brightling, Melanie Calvert, Jenny Camaradou, Nishi Chaturvedi, Amy Chong, Emma Dalrymple, Rosalind M. Eggo, Paul Elliott, Rachael A. Evans, Andy Gibson, Shamil Haroon, Emily Herrett, Linzy Houchen-Wolloff, Sarah E. Hughes, Flic Jeyes, Karen Matthews, Christel McMullan, Jessica Morley, Roz Shafran, Nikki Smith, David Stanton, Terence Stephenson, Jonathan Sterne, Grace M. Turner, Helen Ward, Kamlesh Khunti
Journal: Nature Medicine (2023)
Evaluation of bleeding events in patients receiving acalabrutinib therapy
Authors: Pooja S. Kumar, Tracy Wiczer, Lindsay Rosen, Arthur J. Pollauf, Amy Zheng, Marilly Palettas, Leylah Azali, Seema A. Bhat, John C. Byrd, Michael R. Grever, Kerry A. Rogers, Jennifer A. Woyach, Adam S. Kittai
Journal: Leukemia (2023)
Reply to Havan <i>et al</i>.
Authors: Samer Abu-Sultaneh, Robinder G. Khemani
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: Pediatric Ventilator Liberation Guideline: Should the T-Piece and Automatic Tube Compensation Be Ignored in the Spontaneous Breathing Trial?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Vaccinations in pregnancy against TORCH pathogens
Authors: Ofer Beharier, Michal Neeman
Journal: Molecular Therapy (2023)

Infection during pregnancy is a major concern even for common pathogens, leading to significant maternal and neonatal morbidity, including for those pathogens that rarely infect the fetus by vertical transmission. 1 Argueta L.B. Lacko L.A. Bram Y. Tada T. Carrau L. Rendeiro A.F. Zhang T. Uhl S. Lubor B.C. Chandar V. et al. Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy. iScience. 2022; 25: 104223https://doi.org/10.1016/j.isci.2022.104223 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar However, the risk for congenital developmental defects is significantly elevated for vertically transmitted pathogens, including Zika and the TORCH pathogens. 2 Kumar M. Saadaoui M. Al Khodor S. Infections and pregnancy: effects on maternal and child health. Front. Cell. Infect. Microbiol. 2022; 12: 873253https://doi.org/10.3389/fcimb.2022.873253 Crossref PubMed Scopus (11) Google Scholar The recent COVID-19 pandemic highlighted the elevated risk of infection for pregnant women, and the significant advantage of vaccinating pregnant populations to limit morbidity. 3 Male V. SARS-CoV-2 infection and COVID-19 vaccination in pregnancy. Nat. Rev. Immunol. 2022; 22: 277-282https://doi.org/10.1038/s41577-022-00703-6 Crossref PubMed Scopus (70) Google Scholar However, it also drew attention to the exclusion of pregnant women from clinical trials, implying that the first exposure of this vulnerable population occurred in real-life vaccination campaigns.
Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-κB signaling in vivo
Authors: Xiaojuan Xiao, Zekang Ma, Zhenzhen Li, Yiyi Deng, Yibin Zhang, Ruohong Xiang, Lin Zhu, Yilang He, Hui Li, Yu Jiang, Yu Zhu, Yifang Xie, Hongling Peng, Xifeng Liu, Haiqin Wang, Mao Ye, Yuetao Zhao, Jing Liu
Journal: Biomaterials (2023)
mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
Authors: Irene Olivera, Elixabet Bolaños, Jose Gonzalez-Gomariz, Sandra Hervas-Stubbs, Karina V. Mariño, Carlos Luri-Rey, Iñaki Etxeberria, Assunta Cirella, Josune Egea, Javier Glez-Vaz, Saray Garasa, Maite Alvarez, Iñaki Eguren-Santamaria, Sonia Guedan, Miguel F. Sanmamed, Pedro Berraondo, Gabriel A. Rabinovich, Alvaro Teijeira, Ignacio Melero
Journal: Cell Reports Medicine (2023)

Interleukin-12 (IL-12) gene transfer enhances the therapeutic potency of adoptive T cell therapies. We previously reported that transient engineering of tumor-specific CD8 T cells with IL-12 mRNA enhanced their systemic therapeutic efficacy when delivered intratumorally. Here, we mix T cells engineered with mRNAs to express either single-chain IL-12 (scIL-12) or an IL-18 decoy-resistant variant (DRIL18) that is not functionally hampered by IL-18 binding protein (IL-18BP). These mRNA-engineered T cell mixtures are repeatedly injected into mouse tumors. Pmel-1 T cell receptor (TCR)-transgenic T cells electroporated with scIL-12 or DRIL18 mRNAs exert powerful therapeutic effects in local and distant melanoma lesions. These effects are associated with T cell metabolic fitness, enhanced miR-155 control on immunosuppressive target genes, enhanced expression of various cytokines, and changes in the glycosylation profile of surface proteins, enabling adhesiveness to E-selectin. Efficacy of this intratumoral immunotherapeutic strategy is recapitulated in cultures of tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells on IL-12 and DRIL18 mRNA electroporation.
Discontinuation and reinitiation of SGLT-2 inhibitors and GLP-1R agonists in patients with type 2 diabetes: a nationwide study from 2013 to 2021
Authors: Mariam Elmegaard Malik, Alexander Christian Falkentoft, Jesper Jensen, Deewa Zahir, Saaima Parveen, Amna Alhakak, Charlotte Andersson, Mark C Petrie, Naveed Sattar, John J V McMurray, Lars Køber, Morten Schou
Journal: The Lancet Regional Health - Europe (2023)

Small observational studies have observed poor persistency to sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and glucacon-like-peptide-1-receptor agonists (GLP1-RA), contrary to what has been reported in clinical trials. Therefore, we investigated the risk of discontinuing SGLT2-is and GLP1-RAs in patients with type 2 diabetes (T2D) in a nationwide population.From Danish nationwide registers, all first-time users of SGLT2-is and GLP1-RAs from 2013 to 2021 were identified. Adherence over the first year of therapy, the five-year risk of discontinuing therapy for the first time and the subsequent one-year probability of reinitiating therapy, was assessed. The Aalen-Johansen estimator was used to account for censoring and competing risks and multivariable Cox regression models were used to identify covariates associated with discontinuation.A total of 77,745 first-time users of SGLT2-is (64% male, median age 64 [interquartile range 56-72]) and 56,037 first-time users of GLP1-RAs (56% male, median age 61 [53-70]) were included. The absolute five-year risk of discontinuing therapy was 56% (95% CI: 55-57) and 45% (45-46) for SGLT2-i- and GLP1-RA users, respectively, with a significantly decreased risk over the period studied. The subsequent one-year probability of reinitiating therapy was 24% (95% CI: 24-25) for initial SGLT2-i users and 26% (25-27) for GLP1-RA users.Approximately half of the users of SGLT2-is and GLP1-RAs discontinued therapy within five years, respectively. However, a large proportion of these patients reinitiated therapy during the following year. Further insight into the reasons for discontinuation and initiatives to reduce the time to reinitiation in eligible patients are warranted.The work was funded by an unrestricted research grant from 'Department of Cardiology, Herlev and Gentofte University Hospital'.
Clinical outcomes of the severe acute respiratory syndrome coronavirus 2 Omicron and Delta variant: systematic review and meta-analysis of 33 studies covering 6 037 144 coronavirus disease 2019–positive patients
Authors: Fei-Hong Hu, Yi-Jie Jia, Dan-Yan Zhao, Xue-Lei Fu, Wan-Qing Zhang, Wen Tang, Shi-Qi Hu, Hua Wu, Meng-Wei Ge, Wei Du, Wang-Qin Shen, Bin Zhu, Hong-Lin Chen
Journal: Clinical Microbiology and Infection (2023)

BackgroundAlthough the SARS-CoV-2 Omicron variant is considered to induce less severe disease, there have been no consistent results on the extent of the decrease in severity.ObjectivesTo compare the clinical outcomes of COVID-19–positive patients with Omicron and Delta variant infection.Data sourcesSearches were implemented up to 8 November 2022 in PubMed, Web of Science, BioRvix, and MedRvix.Study eligibility criteriaEligible studies were cohort studies reporting the clinical outcomes of COVID-19–positive patients with Omicron and Delta variant infection, including hospitalization, intensive care unit (ICU) admission, receiving invasive mechanical ventilation (IMV), and death.ParticipantsCOVID-19–positive patients with Omicron and Delta variant infection.Assessment of risk of biasRisk of bias was assessed employing the Newcastle-Ottawa Scale.Methods of data synthesisRandom-effect models were employed to pool the ORs and 95% CIs to compare the risk of clinical outcome. I2 was employed to evaluate the heterogeneity between studies.ResultsA total of 33 studies with 6 037 144 COVID-19–positive patients were included in this meta-analysis. In the general population of COVID-19–positive patients, compared with Delta, Omicron variant infection resulted in a decreased risk of hospitalization (10.24% vs. 4.14%, OR = 2.91, 95% CI = 2.35–3.60), ICU admission (3.67% vs. 0.48%, OR = 3.64, 95% CI = 2.63–5.04), receiving IMV (3.93% vs. 0.34%, OR = 3.11, 95% CI = 1.76–5.50), and death (2.40% vs. 0.46%, OR = 2.97, 95% CI = 2.17–4.08). In the hospitalized patients with COVID-19, compared with Delta, Omicron variant infection resulted in a decreased risk of ICU admission (20.70% vs. 12.90%, OR = 1.63, 95% CI = 1.32–2.02), receiving IMV (10.90% vs. 5.80%, OR = 1.65, 95% CI = 1.28–2.14), and death (10.72% vs. 7.10%, OR = 1.44, 95% CI = 1.22–1.71).ConclusionsCompared with Delta, the severity of Omicron variant infection decreased.
Serpin B9 controls tumor cell killing by CAR T cells
Authors: Thomas Kimman, Anne Slomp, Anne Martens, Sarah Grabherr, Shuang Li, Eline van Diest, Jan Meeldijk, Jurgen Kuball, Monique C Minnema, Eric Eldering, Niels Bovenschen, Zsolt Sebestyén, Victor Peperzak
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Initial clinical responses with gene engineered chimeric antigen receptor (CAR) T cells in cancer patients are highly encouraging; however, primary resistance and also relapse may prevent durable remission in a substantial part of the patients. One of the underlying causes is the resistance mechanisms in cancer cells that limit effective killing by CAR T cells. CAR T cells exert their cytotoxic function through secretion of granzymes and perforin. Inhibition of granzyme B (GrB) can underlie resistance to T cell-mediated killing, and it has been shown that serine proteinase inhibitor serpin B9 can effectively inhibit GrB. We aimed to determine whether expression of serpin B9 by cancer cells can lead to resistance toward CAR T cells. Methods Serpin B9 gene and protein expression were examined by R2 or DepMap database mining and by western blot or flow cytometric analysis, respectively. Coculture killing experiments were performed with melanoma cell line MeWo, diffuse large B cell lymphoma (DLBCL) cell line OCI-Ly7 or primary chronic lymphocytic leukemia (CLL) cells as target cells and natural killer cell line YT-Indy, CD20 CAR T cells or CD19 CAR T cells as effector cells and analyzed by flow cytometry. Results Serpin B9 protein expression was previously shown to be associated with clinical outcome in melanoma patients and in line with these observations we demonstrate that enforced serpin B9 expression in melanoma cells reduces sensitivity to GrB-mediated killing. Next, we examined serpin B9 expression in a wide array of primary tumor tissues and human cell lines to find that serpin B9 is uniformly expressed in B-cell lymphomas and most prominently in DLBCL and CLL. Subsequently, using small interfering RNA, we silenced serpin B9 expression in DLBCL cells, which increased their sensitivity to CD20 CAR T cell-mediated killing. In addition, we showed that co-ulture of primary CLL cells with CD20 CAR T cells results in selection of serpin B9-high CLL cells, suggesting these cells resist CAR T-cell killing. Conclusions Overall, the data indicate that serpin B9 is a resistance mediator for CAR T cell-mediated tumor cell killing that should be inhibited or bypassed to improve CAR T-cell responses.
What's on the horizon for community-based conservation? Emerging threats and opportunities
Authors: Nafeesa Esmail, Jana M. McPherson, Latoya Abulu, Thora Amend, Ronit Amit, Saloni Bhatia, Dominique Bikaba, Typhenn A. Brichieri-Colombi, Jessica Brown, Victoria Buschman, Michael Fabinyi, Mohammad Farhadinia, Razieh Ghayoumi, Terence Hay-Edie, Vera Horigue, Vainuupo Jungblut, Stacy Jupiter, Aidan Keane, David W. Macdonald, Shauna L. Mahajan, Andrew McVey, Axel Moehrenschlager, Fred Nelson, Meher M. Noshirwani, Yaa Ntiamoa-Baidu, Jose Luis Postigo, Vatosoa Rakotondrazafy, Madhu Rao, Dilys Roe, José Antonio Sierra Huelsz, Sue Stolton, Alifereti Tawake, Bonnie Wintle
Journal: Trends in Ecology & Evolution (2023)

Community-based conservation can support livelihoods and biodiversity, while reinforcing local and Indigenous values, cultures, and institutions. Its delivery can help address cross-cutting global challenges, such as climate change, conservation, poverty, and food security. Therefore, understanding trends in community-based conservation is pertinent to setting and implementing global goals. We undertook a horizon scan to prioritize 15 emerging threats and opportunities expected to impact the future effectiveness of community-based conservation. Topics relate to global biodiversity policy; human rights; shifting human geography; inclusion, diversity, equity, and access; conservation finance and income; and economic reforms. Our findings offer guidance on strengthening community-based conservation to achieve global environmental and development goals.
Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials: Based on the mechanisms of occurrence and development of adhesions
Authors: Jie Liao, Xiaoming Li, Yubo Fan
Journal: Bioactive Materials (2023)

Postoperative adhesion (POA) widely occurs in soft tissues and usually leads to chronic pain, dysfunction of adjacent organs and some acute complications, seriously reducing patients' quality of life and even being life-threatening. Except for adhesiolysis, there are few effective methods to release existing adhesion. However, it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence. Hence, preventing POA formation has been regarded as the most effective clinical strategy. Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers. Nevertheless, even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent, thoroughly preventing POA formation is still challenging. Meanwhile, most biomaterials for POA prevention were designed based on limited experiences, not a solid theoretical basis, showing blindness. Hence, we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development. We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues, and named them as "membranous adhesion", "vascular adhesion", "adhesive adhesion" and "scarred adhesion", respectively. Then, the process of the occurrence and development of POA were analyzed, and the main influencing factors in different stages were clarified. Further, we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors. Meanwhile, the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.
Tumor cell integrin β4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo
Authors: Sandra Genduso, Vera Freytag, Daniela Schetler, Lennart Kirchner, Alina Schiecke, Hanna Maar, Daniel Wicklein, Florian Gebauer, Katharina Bröker, Christine Stürken, Karin Milde-Langosch, Leticia Oliveira-Ferrer, Franz L. Ricklefs, Florian Ewald, Gerrit Wolters-Eisfeld, Kristoffer Riecken, Ludmilla Unrau, Linda Krause, Hanibal Bohnenberger, Anne Offermann, Sven Perner, Susanne Sebens, Katrin Lamszus, Linda Diehl, Stefan Linder, Manfred Jücker, Udo Schumacher, Tobias Lange
Journal: Journal of Hematology & Oncology (2023)

Abstract Background The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin β4 (ITGB4) on tumor cells and E-/P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment. Methods We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic immune cell composition were determined by flow cytometry and immunohistochemistry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays. Results We observed a very robust synergism between ITGB4 and E-/P-selectin for the regulation of tumor growth, accompanied by an increased recruitment of CD11b + Gr-1 Hi cells with low granularity (i.e., myeloid-derived suppressor cells, MDSCs) specifically into ITGB4-depleted tumors. ITGB4-depleted tumors undergo apoptosis and actively attract MDSCs, well-known to promote tumor growth in several cancers, via increased secretion of different chemokines. MDSC trafficking into tumors crucially depends on E-/P-selectin expression. Analyses of clinical samples confirmed an inverse relationship between ITGB4 expression in tumors and number of tumor-infiltrating leukocytes. Conclusions These findings suggest a distinct vulnerability of ITGB4 Lo tumors for MDSC-directed immunotherapies. Graphical Abstract
Involvement of inflammasomes in tumor microenvironment and tumor therapies
Authors: Ziqi Zhang, Xue Li, Yang Wang, Yuquan Wei, Xiawei Wei
Journal: Journal of Hematology & Oncology (2023)

Abstract Inflammasomes are macromolecular platforms formed in response to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns, whose formation would cause maturation of interleukin-1 (IL-1) family members and gasdermin D (GSDMD), leading to IL-1 secretion and pyroptosis respectively. Several kinds of inflammasomes detecting different types of dangers have been found. The activation of inflammasomes is regulated at both transcription and posttranscription levels, which is crucial in protecting the host from infections and sterile insults. Present findings have illustrated that inflammasomes are involved in not only infection but also the pathology of tumors implying an important link between inflammation and tumor development. Generally, inflammasomes participate in tumorigenesis, cell death, metastasis, immune evasion, chemotherapy, target therapy, and radiotherapy. Inflammasome components are upregulated in some tumors, and inflammasomes can be activated in cancer cells and other stromal cells by DAMPs, chemotherapy agents, and radiation. In some cases, inflammasomes inhibit tumor progression by initiating GSDMD-mediated pyroptosis in cancer cells and stimulating IL-1 signal-mediated anti-tumor immunity. However, IL-1 signal recruits immunosuppressive cell subsets in other cases. We discuss the conflicting results and propose some possible explanations. Additionally, we also summarize interventions targeting inflammasome pathways in both preclinical and clinical stages. Interventions targeting inflammasomes are promising for immunotherapy and combination therapy.